This invention relates to recirculation washing of blood cells using a spinning membrane filter, and in particular to recirculation washing of blood cells in a magnetic cell selection apparatus.
Fischel U.S. Pat. No. 5,034,135, issued Jul. 23, 1991, and Schoendorfer U.S. Pat. No. 5,053,121, issued Oct. 1, 1991 disclose spinning membrane filters comprising a cylindrical housing and concentric grooved cylindrical rotor. The rotor is covered with a membrane the membrane is spaced from the inner wall of the housing. Blood is introduced into the gap between the membrane and housing. Filtrate passes through the membrane, into the grooves of the rotor, into tubes which communicate with the grooves, and out the bottom center of the spinning membrane filter. Concentrated cells are removed from the gap. FIGS. 7 and 8 in the Fischel patent illustrate a cell washing modification in which a porous wall is interposed between the membrane and the inner wall of the housing. Blood is introduced into the gap between the membrane and the porous wall and an isotonic wash solution is introduced into the gap between the porous wall and the inner wall of the housing. FIG. 6 in the Schoendorfer patent illustrates introduction of a rinse solution with the blood. Schoendorfer et al. U.S. Pat. No. 5,035,121, issued Oct. 1, 1991, discloses use of two spinning membrane filters in series or parallel. A washing solution is introduced into at least one of the spinning membrane filters.
Duff U.S. Pat. No. 5,234,608, issued Aug. 10, 1993, discloses a spinning membrane filter of the type which is preferred for use in conjunction with this invention. According to the disclosure, cell-rich concentrate is removed from the upper portion of the gap between the membrane and the inner wall of the housing, cell-poor plasma filtrate is removed from the bottom center of the spinning membrane filter. Source cell suspension is mixed with cell-rich concentrate and introduced to the lower portion of the gap area.
Schoendorfer et al. U.S. Pat. No. 4,675,106, issued Jun. 23, 1987, U.S. Pat. No. 4,753,729, issued Jun. 28, 1988, and U.S. Pat. No. 4,816,151, issued Mar. 28, 1989, disclose drive mechanisms for spinning membrane filters.
Moubayed et al. U.S. Pat. No. 5,536,475 discloses a semi-automated instrument for selection of blood cells using paramagnetic beads which are coated with a binding agent such as an antibody which binds specifically to the cells to be selected. The instrument comprises a primary magnet associated with a primary container and a secondary magnet associated with a secondary container. Blood cells, liquid and beads are agitated in the primary container to form a conjugate between the beads and the selected cells. The primary magnet is then moved into a position adjacent the primary container to magnetically capture the bead/cell conjugate and the non-selected cells and liquid are removed. The primary magnet is then moved into a position away from the primary container to release the bead/cell conjugate. Wash solution is added and the contents of the primary container are agitated, then the primary magnet is moved into the position adjacent the primary container to again capture the bead/cell conjugate and the wash solution is removed. The primary magnet is again moved into a position away from the primary container to release the bead/cell conjugate. Liquid containing a reagent which releases the selected cells from the beads is added and the contents are again agitated. The primary magnet is again moved into the position adjacent the primary container to capture the beads. The released cells and liquid are introduced to the secondary container. The secondary container is positioned adjacent to the secondary magnet to capture any beads which may have escaped the primary magnet. The instrument is used with a disposable set comprising plastic bags for wash liquid, cell suspension and bead suspension, interconnected with plastic tubing.
The semi-automated instrument disclosed in the Moubayed et al. patent is sold by Baxter Healthcare Corporation, under the trademark Isolext.RTM. 300 SA. A modified version of the instrument is sold by the Baxter Healthcare Corporation under the trademark Isolex.RTM. 300i. The 300i differs from the 300 SA in that it is fully automated and it includes a spinning membrane filter for washing the selected cells and also for removing platelets from the source cells prior to selection.
Chapman et al. International Publication WO 95/13837, published May 26, 1995, discloses a peristaltic pumping assembly of a type which is used to move fluids in the Isolex.RTM. 300 SA and Isolex.RTM. 300i instruments. Deniega et al. International Publication WO 95/14172, published May 26, 1995, discloses an organizer frame of a type which is used with the peristaltic pumping assembly in the Isolex.RTM. 300 SA and Isolex.RTM. 300i instruments. The organizer frame is also used on a machine for separation of platelets from whole blood. Deniega discloses a tubing set which includes a spinning membrane filter and a reservoir for platelet-poor packed blood cells. The reservoir has a top and bottom port. Packed cells from the outlet of the spinning membrane filter enter through the top inlet port of the reservoir. Whole blood from a patient enters through the bottom inlet port.
Recirculation washing of selected blood cells is performed in the Isolex.RTM. 300i utilizing the spinning membrane filter in conjunction with a recirculation wash bag which has both inlet and outlet ports at the bottom and no port at the top. The bag is a 600 ml bag with the inlet and outlet ports separated by about 2 inches. The bag has been able to concentrate cell suspensions that normally start at about 400 ml. This bag performed better when it was occasionally massaged. This is the only way to process more than about 5.times.10.sup.10 cells in the bag.
The above-cited U.S. patent and International Publications are each incorporated herein by reference.